Quinazoline antifolates, already available, as well as new compounds that will be synthesized by Dr. John Hynes of the University of South Carolina School of Medicine will be evaluated as inhibitors of thymidylate synthetase and dihydrofolate reductase from human adenocarcinoma cells grown in culture. Compounds that inhibit thymidylate synthetase will be further tested for their ability to enhance 5 fluoro-deoxyuridylate (FdUMP) binding to thymidylate synthetase. On the basis of these tests, promising compounds will be tested as inhibitors of growth of human adenocarcinoma cells grown in tissue culture alone and in the presence of 5 fluoracil and flurodeoxyuridine. Candidate compounds will also be tested against mice bearing a transplantable carcinogen-induced adenocarcinomas, and effects of the compounds will be monitored by following the incorporation of 3H-deoxyuridine into DNA of tumor, intestinal mucosa and marrow.